Esophageal cancer is one of the least studied and deadliest cancers in the world and is the 7th leading cause of cancer death among American men. Tobacco smoke and gastroesophageal reflux are the most important risk factors in esophageal carcinogenesis. Over past 10 years, we have built up extensive experiences working on esophageal cancer. For example, we have demonstrated lost expression of RAR-beta2 in premalignant and malignant esophageal tissues as compared to normal tissues and detection of RAR-beta2 expression as a biomarker for different clinical chemoprevention studies by researchers at our institution and by other groups. Furthermore, we found that BPDE (a carcinogen present in tobacco smoke and environment pollution) and tumor-promoting bile acid suppressed RAR-beta2 expression and induced expression of EGFR, AP-1, COX-2, and phosphorylated Erk1/2 in premalignant and malignant esophageal cells. In this application, our preliminary data have shown that expression of the selected miRNAs is altered in esophageal cancer tissue specimens compared to the normal tissues. miRNAs play important roles in cell growth, apoptosis, differentiation, and tumorigenesis but are differentially expressed in various cancer tissues and cells. We, therefore, hypothesize that miRNAs, an abundant class of small noncoding RNAs of 18-22 nucleotides in length, act as posttranslational silence of target gene expression and altered expression of miRNAs could result in esophageal cancer development and progression; thus, identification of such alterations may provide biomarkers for early detection or prognosis and perhaps also provide targets for novel preventive and therapeutic strategies for esophageal cancer. To test our hypothesis, we have proposed the following Specific Aims: 1) To determine differential expression of miRNAs as bipmarkers for early detection and prognosis of esophageal cancer by using tissue arrays from normal, premalignant, and malignant esophageal specimens and from esophageal cancer specimens with patients' follow-up data, and 2) To investigate the role of miRNAs (selected from Aim 1) in regulating esophageal cancer cell growth, apoptosis, and transformation and explore the underlying molecular mechanisms of their alterations in esophageal cancer. We expect to provide an initial assessment of altered expression of miRNAs as biomarker for early detection and prognosis of esophageal cancer and to provide a novel insight into their role in esophageal cell growth, apoptosis, and transformation. [unreadable] [unreadable] [unreadable]